1989 Fiscal Year Annual Research Report

成人T細胞白血病と病因ウイルス

Research Project

Project/Area Number	01010006
Research Institution	Tohoku University
Principal Investigator	菅村和夫東北大学, 医学部, 教授 (20117360)
Co-Investigator(Kenkyū-buntansha)	戸澤秀樹北里大学, 衛生学部, 教授 (90104562) 宮本勉長崎大学, 医学部, 教授 (10004582) 星野洪郎群馬大学, 医学部, 教授 (00107434) 速水正憲京都大学, ウイルス研究所, 教授 (40072946) 園田俊郎鹿児島大学, 医学部, 助教授 (40036463)
Keywords	成人T細胞白血病 / HTLVーI / p40^<tax> / DNA結合因子 / 抗HTLVーI抗体 / 感染防御
Research Abstract	本研究班では(1)HVLVーIによる発癌分子機構(2)HTLVーI感染防御機構、(3)成人T細胞白血病(ATL)発症のモデル動物実験系に関する研究を行っている。本年度はHTLVーI発癌分子機構の中で特にp40^<tax>の機能解析について大きな進展がみられた。HTLVーIのpX遺伝子にコードされるp40^<tax>は、ウイルス自身の遺伝子ばかりではなく、種々の細胞側遺伝子の転写活性を誘導するが、DNAへの直接の結合能はない。そこで、トランス活性化を仲介する細胞性因子の検索が行われた。まずp40^<tax>の標的配列であるHTLVーI LTR内の21塩基配列に直接結合する細胞性因子のcDNAクローニングが行われ、癌研で3種、癌センターで5種の遺伝子が同定された。これらの蛋白は、ロイシンジッパー及び塩基性領域を持ち、DNA結合蛋白に特徴的構造を持っていた。また、p40^<tax>と結合する細胞性因子が検索され、抗p40^<tax>抗体を用いた免疫沈降法によりp40^<tax>と特異的に共沈する2種の蛋白(p60、p95)が同定された。p60は一部アミノ酸配列が決定され、遺伝子クローニングが試みられている(東北大、医)。他方、家兎を用いたin vivo感染実験系において、HTLVーI抗体陽性ヒトIgG投与によるHTLVーI感染防御効果が明らかにされた。家兎にHTLVーI陽性血液を注入するとHTLVーI感染が成立するが、注入後24時間以内にヒト抗HTLVーI IgG抗体を投与することによって感染を完全に防御することができた。これらの結果から、ヒト抗HTLVーI IgG抗体が感染初期には有効な防御手段と成り得るものと考えられる。

Research Products

(47 results)

All Other

All Publications (47 results)

[Publications] Ohtani,K.: "Electroporation:application to human lymphoid cell lines for stable introduction of a transactivator gene of human T-cell leukemia virus type I" Nuclic Acids Res.17. 1589-1604 (1989)
[Publications] Nakamura,M.: "Regulation of the promoter activity of human T-cell leukemia virus type I" UCLA Symposia on Molecular and Cellular Biology,New Series. 87. 103-116 (1989)
[Publications] Nagata,K.: "Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40^<tax> protein in a human T-cell line Jurkat" J.Virol.63. 3220-3226 (1989)
[Publications] Nakamura,M.: "Differential activation of the 21-base-pair enhancer element of human T-cell leukemia virus type I by its own trans-activator and cyclic AMP" Nuclic Acids Res.17. 5207-5221 (1989)
[Publications] Saito,S.: "Detection of HTLV-I genome in seronegative infants born to HTLV-I genome in seronegative infants born to HTLV-I seropositive mothers by polymerase chain reaction" Jpn.J.Cancer Res.80. 808-812 (1989)
[Publications] Nakamura,M.: "Cell line-dependent response of the enhancer element of simian virus 40 to transactivator p40^<tax> encoded by human T-cell leukemia virus type I" J.Biol.Chem.264. 20189-20192 (1989)
[Publications] Fujisawa,J.: "A unique enhancer element for the transactivator(p40^<tax>)of human T-cell leukemia virus type I that is distinct from cyclic AMP-and 12-O-tetradecanoylphorbol-13-acetate-responsive elements" J.Virol.63. 3234-3239 (1989)
[Publications] Maekawa,T.: "Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain" EMBO J.8. 2023-2028 (1989)
[Publications] Furuta,Y.: "Thymic atrophy characteristic in transgenic mice that harbor pX genes of HTLV-I" J.Virol.63. 3185-3189 (1989)
[Publications] Arai,N.: "Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression" J.Immunol.142. 274-282 (1989)
[Publications] Hatanaka,M.: "Viral proteinases as targets for chemotherapy.Process of gag-propolyprotein by HTLV-I proteinase." Current Communications in Molecular Biology. 117-126 (1989)
[Publications] Hatanaka,M.: "Identification of HTLV-I gag protease and its sequential processing of the gag gene product" J.Cell.Biochem.40. 15-30 (1989)
[Publications] Kawanishi,T.: "Low-titer antibodies reactive with HTLV-I gag p19 in patients with chronic myeloneuropathy" Ann.Nerol.26. 515-522 (1989)
[Publications] Kubota,S.: "Functional similarity of HIV-I rev and HTLV-I rex proteins:Identification of a new nucleolar-targeting in rev protein" BBRC. 162. 963-970 (1989)
[Publications] Maki,M.: "Inhibition of calpain by a synthetic oligopeptide corresponding to an exon of the human calpastatin gene" J.Biol.Chem.264. 18866-18869 (1989)
[Publications] Murachi,T.: "Cloning and expression of the genes for calpains and calpastatins" Biochem.Soc.Symp.UK. 55. 29-44 (1989)
[Publications] Nosaka,T.: "Nucleolar targeting signal of human T-cell leukemia virus type I rex-encoded protein is essential for cytoplasmic accumulation of unspliced viral mRNA" Proc.Natl.Acad.Sci.USA. 86. 9798-9802 (1989)
[Publications] Zhou,Z.: "Expression of post-transcriptional regulatory gene of HTLV-I,rex,in Escherichia coli" Virus Genes. 3. 153-158 (1989)
[Publications] Hoshino,H.: "New antifungal antibiotics,benanomicins A and B inhibit infection of T-cell with human immunodeficiency virus(HIV)and syncytium formation by HIV" J.Antibiotics. 42. 344-346 (1989)
[Publications] Seki,J.: "Inhibition of infectivity of human immunodeficiency virus by a novel nucleoside,oxethanocin,and related compounds" Antimicrobial Agents and Chemotherapy. 33. 773-775 (1989)
[Publications] Suetake,N.: "Frequent lack of antibodies against human T-cell leukemia virus type I gag proteins p24 or p19 in sera of patients with adult T-cell leukemia" J.Cancer Res.Clin.Oncol.115. 279-284 (1989)
[Publications] Sakamoto,K.: "Potential usefullness of a cultured glioma cell line induced by Rous sarcoma virus in B10.A mouse as an immunotherapy model." Jpn.J.Exp.Med.59. 173-180 (1989)
[Publications] Okamoto,T.: "Multi-step carcinogenesis model for adult T-cell leukemia" Jpn.J.Cancer Res.80. 191-195 (1989)
[Publications] Kinoshita,T.: "Detection of mRNA of the tax/rex gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction" Proc.Natl.Acad.Sci.USA. 80. 5620-5624 (1989)
[Publications] Tanaka,Y.: "Heterogeneity of antigen molecules recognized by anti-tax monoclonal antibody Lt-4 in cell lines bearing human T cell leukemia virus type I and its related retroviruses" Jpn.J.Cancer Res.
[Publications] Ikeda,S.: "Detection of preleukemic state of adult T-cell leukemia(Pre-ATL)in HTLV-I carriers" Cancer Detection and Prevention.
[Publications] Kamihira,S.: "Immunoglobulin classes of antibody for human T-lymphotropic virus type I(HTLV-I)in healthy donors and HTLV-I-associated disorders" Vox Sanguinis. 56. 168-173 (1989)
[Publications] Hamatani,K.: "Increased expression of ras genes in non-hodgkin's lymphoma is not associated with oncogenic activation of those genes by point mutation" Jpn.J.Cancer Res.80. 706-710 (1989)
[Publications] Kamihira,S.: "Antibodies against p40^<tax> gene product of human T-lymphotropic virus type I(HTLV-I)under various conditions of HTLV-I infection" Jpn.J.Cancer Res.80. 1066-1071 (1989)
[Publications] Sonoda,S.: "Immunological aspects of HTLV-I infections" Neurol.Nerobiol.51. 277-286 (1989)
[Publications] Sonoda,S.: "HLA and Immunological aspects of HTLV-I-associated myelopathy(HAM)" Neurol.Neurobiol.51. 297-304 (1989)
[Publications] Yoshida,M.: "Increased replication of HTLV-I in HTLV-I associated myelopathy" Ann.Neurol.21. 331-335 (1989)
[Publications] Ueda,K.: "Cohort effect on HTLV-I seroprevalence in Southern Japan" Lancet. ii. 979 (1989)
[Publications] Gotoh,H.: "A human ecological study on epidemics of HBV and HTLV-I among islands in western Japan" Acta Med.Nagasaki. 34. 28-31 (1989)
[Publications] Nomata,K.: "Expression of ras gene family as result of compensatory renal growth in mice" Urological Res.
[Publications] Nakayama,D.: "Amplification of HTLV-1 related sequences among patients with neurological disorders in highly endemic Nagasaki:Lack of evidence for association of HTLV-1 with multiple sclerosis" Jpn.J.Cancer Res.
[Publications] Takehara,N.: "Effect of immunization on HTLV-I infection in rabbits" Int.J.Cancer. 44. 332-336 (1989)
[Publications] Sawada,T.: "High risk of mother-to-child transmission of HTLV-I in p40^<tax> antibody-positive mothers" Jpn.J.Cancer Res.80. 506-508 (1989)
[Publications] Fukumoto,S.: "Secretion of parathyroid hormone-like activity from human T-cell lymphotropic virus type I-infected lymphocytes" Cancer Res.49. 3849-3852 (1989)
[Publications] Chen,Y.A.: "Antibody reactivity to different regions of human T-cell leukemia virus type I gp61 in infected people" J.Virol.63. 4952-4957 (1989)
[Publications] Cockerell,G.L.: "Infection of rabbits with HTLV-I:patterns of anti-viral antibody reactivity and detection of virus by gene amplification" Int.J.Cancer.
[Publications] Yoshimura,N.: "Killer cell systems of cynomolgus monkeys experimentally infected with HTLV-I" J.Immunol.142. 1970-1974 (1989)
[Publications] Hasegawa,A.: "Sequence of a distinct HIV-2 isoalted from Ghana showing significant divergence" AIDS and Human Retro Virus. 5. 593-604 (1989)
[Publications] Kawamura,M.: "Immunological reactivities of Ghanaian sera with HIV-1,HIV-2" AIDS. 3. 609-611 (1989)
[Publications] Hatanaka,M.: "“Synthesis and activity of HTLV-I protease and its muteins" Proteases of Retroviruses(ed.V.Kostka)" Walter de Gruyter,Berlin, pp119-124 (1989)
[Publications] Tujimoto,A.: "“Homology of HTLV-I viral isolates from HTLV-I-associated myelopathy"HTLV-I and the nervous system(Roman,G.C.et al.eds.)" Alan R.Liss,New York, pp43-50 (1989)
[Publications] Takehara,N.: "“Protection of rabbits against HTLV-I infection by passive immunization"Human Retroviruses(Groopman,J.E.eds.)" Alan R.Liss,New York, (1989)

1989 Fiscal Year Annual Research Report

成人T細胞白血病と病因ウイルス

Principal Investigator

菅村 和夫 東北大学, 医学部, 教授 (20117360)

Research Products

[Publications] Ohtani,K.: "Electroporation:application to human lymphoid cell lines for stable introduction of a transactivator gene of human T-cell leukemia virus type I" Nuclic Acids Res.17. 1589-1604 (1989)

[Publications] Nakamura,M.: "Regulation of the promoter activity of human T-cell leukemia virus type I" UCLA Symposia on Molecular and Cellular Biology,New Series. 87. 103-116 (1989)

[Publications] Nagata,K.: "Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40^<tax> protein in a human T-cell line Jurkat" J.Virol.63. 3220-3226 (1989)

[Publications] Nakamura,M.: "Differential activation of the 21-base-pair enhancer element of human T-cell leukemia virus type I by its own trans-activator and cyclic AMP" Nuclic Acids Res.17. 5207-5221 (1989)

[Publications] Saito,S.: "Detection of HTLV-I genome in seronegative infants born to HTLV-I genome in seronegative infants born to HTLV-I seropositive mothers by polymerase chain reaction" Jpn.J.Cancer Res.80. 808-812 (1989)

[Publications] Nakamura,M.: "Cell line-dependent response of the enhancer element of simian virus 40 to transactivator p40^<tax> encoded by human T-cell leukemia virus type I" J.Biol.Chem.264. 20189-20192 (1989)

[Publications] Fujisawa,J.: "A unique enhancer element for the transactivator(p40^<tax>)of human T-cell leukemia virus type I that is distinct from cyclic AMP-and 12-O-tetradecanoylphorbol-13-acetate-responsive elements" J.Virol.63. 3234-3239 (1989)

[Publications] Maekawa,T.: "Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain" EMBO J.8. 2023-2028 (1989)

[Publications] Furuta,Y.: "Thymic atrophy characteristic in transgenic mice that harbor pX genes of HTLV-I" J.Virol.63. 3185-3189 (1989)

[Publications] Arai,N.: "Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression" J.Immunol.142. 274-282 (1989)

[Publications] Hatanaka,M.: "Viral proteinases as targets for chemotherapy.Process of gag-propolyprotein by HTLV-I proteinase." Current Communications in Molecular Biology. 117-126 (1989)

[Publications] Hatanaka,M.: "Identification of HTLV-I gag protease and its sequential processing of the gag gene product" J.Cell.Biochem.40. 15-30 (1989)

[Publications] Kawanishi,T.: "Low-titer antibodies reactive with HTLV-I gag p19 in patients with chronic myeloneuropathy" Ann.Nerol.26. 515-522 (1989)

[Publications] Kubota,S.: "Functional similarity of HIV-I rev and HTLV-I rex proteins:Identification of a new nucleolar-targeting in rev protein" BBRC. 162. 963-970 (1989)

[Publications] Maki,M.: "Inhibition of calpain by a synthetic oligopeptide corresponding to an exon of the human calpastatin gene" J.Biol.Chem.264. 18866-18869 (1989)

[Publications] Murachi,T.: "Cloning and expression of the genes for calpains and calpastatins" Biochem.Soc.Symp.UK. 55. 29-44 (1989)

[Publications] Nosaka,T.: "Nucleolar targeting signal of human T-cell leukemia virus type I rex-encoded protein is essential for cytoplasmic accumulation of unspliced viral mRNA" Proc.Natl.Acad.Sci.USA. 86. 9798-9802 (1989)

[Publications] Zhou,Z.: "Expression of post-transcriptional regulatory gene of HTLV-I,rex,in Escherichia coli" Virus Genes. 3. 153-158 (1989)

[Publications] Hoshino,H.: "New antifungal antibiotics,benanomicins A and B inhibit infection of T-cell with human immunodeficiency virus(HIV)and syncytium formation by HIV" J.Antibiotics. 42. 344-346 (1989)

[Publications] Seki,J.: "Inhibition of infectivity of human immunodeficiency virus by a novel nucleoside,oxethanocin,and related compounds" Antimicrobial Agents and Chemotherapy. 33. 773-775 (1989)

[Publications] Suetake,N.: "Frequent lack of antibodies against human T-cell leukemia virus type I gag proteins p24 or p19 in sera of patients with adult T-cell leukemia" J.Cancer Res.Clin.Oncol.115. 279-284 (1989)

[Publications] Sakamoto,K.: "Potential usefullness of a cultured glioma cell line induced by Rous sarcoma virus in B10.A mouse as an immunotherapy model." Jpn.J.Exp.Med.59. 173-180 (1989)

[Publications] Okamoto,T.: "Multi-step carcinogenesis model for adult T-cell leukemia" Jpn.J.Cancer Res.80. 191-195 (1989)

[Publications] Kinoshita,T.: "Detection of mRNA of the tax/rex gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction" Proc.Natl.Acad.Sci.USA. 80. 5620-5624 (1989)

[Publications] Tanaka,Y.: "Heterogeneity of antigen molecules recognized by anti-tax monoclonal antibody Lt-4 in cell lines bearing human T cell leukemia virus type I and its related retroviruses" Jpn.J.Cancer Res.

[Publications] Ikeda,S.: "Detection of preleukemic state of adult T-cell leukemia(Pre-ATL)in HTLV-I carriers" Cancer Detection and Prevention.

[Publications] Kamihira,S.: "Immunoglobulin classes of antibody for human T-lymphotropic virus type I(HTLV-I)in healthy donors and HTLV-I-associated disorders" Vox Sanguinis. 56. 168-173 (1989)

[Publications] Hamatani,K.: "Increased expression of ras genes in non-hodgkin's lymphoma is not associated with oncogenic activation of those genes by point mutation" Jpn.J.Cancer Res.80. 706-710 (1989)

[Publications] Kamihira,S.: "Antibodies against p40^<tax> gene product of human T-lymphotropic virus type I(HTLV-I)under various conditions of HTLV-I infection" Jpn.J.Cancer Res.80. 1066-1071 (1989)

[Publications] Sonoda,S.: "Immunological aspects of HTLV-I infections" Neurol.Nerobiol.51. 277-286 (1989)

[Publications] Sonoda,S.: "HLA and Immunological aspects of HTLV-I-associated myelopathy(HAM)" Neurol.Neurobiol.51. 297-304 (1989)

[Publications] Yoshida,M.: "Increased replication of HTLV-I in HTLV-I associated myelopathy" Ann.Neurol.21. 331-335 (1989)

[Publications] Ueda,K.: "Cohort effect on HTLV-I seroprevalence in Southern Japan" Lancet. ii. 979 (1989)

[Publications] Gotoh,H.: "A human ecological study on epidemics of HBV and HTLV-I among islands in western Japan" Acta Med.Nagasaki. 34. 28-31 (1989)

[Publications] Nomata,K.: "Expression of ras gene family as result of compensatory renal growth in mice" Urological Res.

[Publications] Nakayama,D.: "Amplification of HTLV-1 related sequences among patients with neurological disorders in highly endemic Nagasaki:Lack of evidence for association of HTLV-1 with multiple sclerosis" Jpn.J.Cancer Res.

[Publications] Takehara,N.: "Effect of immunization on HTLV-I infection in rabbits" Int.J.Cancer. 44. 332-336 (1989)

[Publications] Sawada,T.: "High risk of mother-to-child transmission of HTLV-I in p40^<tax> antibody-positive mothers" Jpn.J.Cancer Res.80. 506-508 (1989)

[Publications] Fukumoto,S.: "Secretion of parathyroid hormone-like activity from human T-cell lymphotropic virus type I-infected lymphocytes" Cancer Res.49. 3849-3852 (1989)

[Publications] Chen,Y.A.: "Antibody reactivity to different regions of human T-cell leukemia virus type I gp61 in infected people" J.Virol.63. 4952-4957 (1989)

[Publications] Cockerell,G.L.: "Infection of rabbits with HTLV-I:patterns of anti-viral antibody reactivity and detection of virus by gene amplification" Int.J.Cancer.

[Publications] Yoshimura,N.: "Killer cell systems of cynomolgus monkeys experimentally infected with HTLV-I" J.Immunol.142. 1970-1974 (1989)

[Publications] Hasegawa,A.: "Sequence of a distinct HIV-2 isoalted from Ghana showing significant divergence" AIDS and Human Retro Virus. 5. 593-604 (1989)

[Publications] Kawamura,M.: "Immunological reactivities of Ghanaian sera with HIV-1,HIV-2" AIDS. 3. 609-611 (1989)

[Publications] Hatanaka,M.: "“Synthesis and activity of HTLV-I protease and its muteins" Proteases of Retroviruses(ed.V.Kostka)" Walter de Gruyter,Berlin, pp119-124 (1989)

[Publications] Tujimoto,A.: "“Homology of HTLV-I viral isolates from HTLV-I-associated myelopathy"HTLV-I and the nervous system(Roman,G.C.et al.eds.)" Alan R.Liss,New York, pp43-50 (1989)

[Publications] Takehara,N.: "“Protection of rabbits against HTLV-I infection by passive immunization"Human Retroviruses(Groopman,J.E.eds.)" Alan R.Liss,New York, (1989)

菅村和夫東北大学, 医学部, 教授 (20117360)